Morphology and molten-state rheology of polylactide and polyhydroxyalkanoate blends

Polylactide (PLA) and poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) blends were prepared at different compositions by melt mixing. First, the rheological properties of each individual component are briefly presented focusing on the most important aspects to be taken into account during blends preparation and investigation. The kinetics of PHBV viscosity decrease due to strong polymer degradation in the molten state was recorded. This helped making a choice of the blending parameters and of the way of performing the rheological frequency sweeps. DSC showed that components are immiscible in the whole range of compositions studied. Blends morphology was studied using high-resolution scanning electron microscope and optical microscopy in reflection mode. Nodular and co-continuous morphologies were observed depending on the composition, and minor phase size was roughly estimated. The rheology of PLA/PHBV blends was investigated in the dynamic mode and correlated with the morphology observed. The results showed an important role of the interfaces between PLA and PHBV and a peculiar behaviour of the viscosity of some mixtures at low frequencies. At medium and high frequencies mixture dynamic viscosity follows the mixing law.     

Improved rapid assay of plasma uric acid by short-end injection capillary zone electrophoresis

A rapid and simple short-end injection capillary zone electrophoresis method was developed for the quantification of plasma uric acid. The separation was performed in an uncoated fused-silica capillary (50 μm ID, 60 cm total length, 10.2 cm effective length) by using as a background electrolyte a 75 mmol/L glycylglycine solution titrated with NaOH 5 mol/L to pH 9.0, a voltage of 28 kV, a cartridge temperature of 15 °C, and direct UV detection at 292 nm. Under optimized conditions, uric acid was determinate in little more than 1 min (1.076 minutes). In order to verify the accuracy of the analysis, urate levels were measured in 543 apparently healthy volunteers by the new assay and our previous method, and the obtained data were compared by Passing–Bablock regression, Bland–Altman test, and a new regression-based approach, which showed a good agreement between two methods.     

Preparation of bis(μ-chalcogeno) complexes [(η5-RC5H4)2M(μ-E)]2 M = Zr,Hf; R = H,t-Bu; E = S or Se from metallocene dichlorides,and isolation of the mixed μ-complexes [(t-BuC5H4)2Zr2](μ-O)(μ-E)

Metallocene dichlorides (RCp)₂MCl₂ (M = Zr, Hf; R = H, t-Bu) react with E/2HLiBEt₃ (E = S, Se) to give the symmetrical dinuclear compounds [(RCp)₂M(μ-E)]₂. UV irradiation in toluene of [(t-BuCp)₂Zr(CH₃)]₂(μ-O) in the presence of powdered sulfur or gray selenium gives the new compounds [(t-BuCp)₂Zr₂](μ-O)(μ-E).     

A small molecule discrimination map of the antibiotic resistance kinome

Kinase-mediated resistance to antibiotics is a significant clinical challenge. These enzymes share a common protein fold characteristic of Ser/Thr/Tyr protein kinases. We screened 14 antibiotic resistance kinases against 80 chemically diverse protein kinase inhibitors to map resistance kinase chemical space. The screens identified molecules with both broad and narrow inhibition profiles, proving that protein kinase inhibitors offer privileged chemical matter with the potential to block antibiotic resistance. One example is the flavonol quercetin, which inhibited a number of resistance kinases in vitro and in vivo. This activity was rationalized by determination of the crystal structure of the aminoglycoside kinase APH(2″)-IVa in complex with quercetin and its antibiotic substrate kanamycin. Our data demonstrate that protein kinase inhibitors offer chemical scaffolds that can block antibiotic resistance, providing leads for co-drug design.     

Bile UPLC-MS fingerprinting and bile acid fluxes during human liver transplantation

Bile flow restoration is a crucial step in the recovery process post transplantation of the liver. Here, metabolic trajectories based on changes in bile secretion - a known marker of functionality - have been utilised as an approach for discovering bile fluxes during transplantation. A total of ten liver transplants were monitored and from these 68 bile samples from both donors and recipients were collected and analysed using ultra-performance LC-MS in combination with multivariate statistical analysis. Based on the principal component scores constructed from the total bile fingerprint, differentiation of the bile acid concentrations before and after transplantation was detected. A trend was also observed, by constructing metabolic trajectories, whereby the post-transplant profiles approached the position of pre-transplant profiles within 30-60?min of the restoration of bile secretion function. The ten major conjugated bile acid salts were measured and a significant increase in concentrations of taurocholic acid and taurochenodeoxycholic acid were seen after transplantation. In addition, the ratios of secondary bile acids detected in gall bladder and hepatic bile were measured before and after transplantation. This study suggests that bile acid ratios in the donor liver at the pre-transplant and post-transplant stage may be important and that profiling of secreted bile after transplantation may aid clinical assessment and progress post-transplantation.     

Time-resolved optical Kerr-effect spectroscopy of low-frequency dynamics in Di-L-alanine,poly-L-alanine,and lysozyme in solution

The low-frequency spectra of peptides and proteins in solution have been investigated with optical heterodyne-detected Raman-induced Kerr-effect spectroscopy. Spectra were obtained for di-l-alanine ALA(2) and poly-l-alanine (PLA) in dichloroacetic acid solution. The conformational dependence of those spectra at low frequency has been analyzed. ALA(2) displays a band centered at 50 cm-1, whereas the alpha-helical PLA shows two shoulders at 60 and 140 cm-1. The similarity of the spectral features observed in PLA to those in water can be explained by analogous acoustic translational modes in the hydrogen network of the PLA alpha-helix. The mostly alpha-helical protein lysozyme in aqueous solution has also been investigated and showed significantly more structure with modes at 10, 35, 73, 106, and 164 cm-1.